Novel gene therapy approach produces pain control in rats
WESTPORT, Apr 29, 1999 (Reuters Health) - Experimental findings in
rats suggest that a new gene therapy approach may help relieve
chronic pain resulting from cancer or arthritis, and may even
provide a mechanism for delivering therapeutic agents to a broad
region of neurons in patients with neurodegenerative diseases.
Dr. Alan A. Finegold, of the National Institutes of Health in
Bethesda, Maryland, and colleagues there and at the University of
Pennsylvania, in Philadelphia, injected an adenovirus encoding
beta-endorphin into the cerebrospinal fluid surrounding the spinal
cord of rats, instead of directly into the spinal cord.
The beta-endorphin transgene was expressed in meningeal pia
mater cells, Dr. Finegold and his team found, with levels peaking
between days 3 and 7 post-injection and waning after 15 days.
The transgene was also expressed in ependymal cells.
"A surprising finding from these experiments on viral delivery of
beta-endorphin concerns the specificity of action towards different
types of pain," the scientists write in the May 1st issue of Human
Gene Therapy.
The investigators induced inflammation in one hind paw of a series
of rats and exposed them to a thermal stimulus. By measuring how
many seconds elapsed before the rats withdrew their paws from
the stimulus, they found that pain sensitivity was significantly
reduced in rats injected with the beta-endorphin transgene
compared with control animals, but only in the inflamed paw.
The finding indicates "...a lack of toxicity or non-specific effects,"
the research team points out.
"The simplicity of this meningeal-paracrine gene therapy approach,
rapidity of expression, ease of application, and apparent lack of
side effects offer the possibility of a more general clinical
utilization," Dr. Finegold and colleagues say in the report.
"So, given the right gene, our approach has application to a broad
range of conditions, from pain control to spinal cord injury and
disorders like multiple sclerosis and Parkinson's disease," coauthor
Dr. Mike Iadarola elaborates in an NIH press release.
Hum Gene Ther 1999;10:1251-1257.
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